Schema di chemioterapia da associare a trastuzumab e valutazione della risposta Laura Biganzoli U.O. Oncologia Medica “Sandro Pitigliani” Ospedale di Prato Istituto Toscano Tumori

Caso clinico Donna di 50 anni ECOG PS0 Nega comorbidita’ Autopalpazione nodulo mammella dx  mammografia: nodulo QSE di 5 cm, Ln ascellare dx: C5; agobiopsia mammaria: B5 CDIS -Carcinoma duttale infiltrante G3, ER 50%, PgR40%, Ki67 30%, HER2 3+; RMN lesione unifocale Non fattibile intervento chirurgico conservativo TC Torace-addome e scintigrafia ossea = negative per M+; ECO cuore=N

Opzioni terapeutiche Si propone alla paziente trattamento neoadiuvante contenente trastuzumab antraciclina  taxano + trastuzumab antraciclina + trastuzumab  taxano + trastuzumab chemioterapia senza antraciclina + trastuzumab nessuna chemioterapia ma “dual HER2 targeting” A+T standard= aumenta pCR rate  better outcome

NSABP B-27 % pCR 13.7 25.6 p<.001 ACx4 Sx Tx4 Arm A Arm B Arm C T, docetaxel Sx, surgery % pCR 13.7 25.6 p<.001 Overall survival Bear et al. J Clin Oncol 2006

MDACC trial pCR, % (95% CI) 26.3 (9-51) 65.2 (43-84) 54.5 (32.2-75.6) Randomized groups Assigned treatment T+FEC (n=19) T+FEC+H (n=23) T+FEC+H (n=22) pCR, % (95% CI) 26.3 (9-51) 65.2 (43-84) 54.5 (32.2-75.6) T, paclitaxel; H, trastuzumab Buzdar et al. Clin Cancer Res 2007 Randomized study population

NOAH: Phase III, Open-Label Trial of Neoadjuvant Trastuzumab Gianni et al. Lancet. 2010

Cardiac safety MDACC No clinical cardiac dysfunction Exact binomial 95% CI of the probability of cardiac failure = 0% to 7.8% Buzdar et al. Clin Cancer Res 2007 NOHA Median follow-up 3.2 yrs Gianni et al. Lancet. 2010

Neo-ALTTO NeoSphere pCR rates pCR rate in NOHA= 43% Baselga et al. Cancer Res 2010 Gianni et al. Cancer Res 2010 pCR rate in NOHA= 43%

NeoSphere Chang et al. Gianni et al. Cancer Res 2010 Chang et al. ASCO 2011

Mia opinione Chemioterapia contenente antracicline e taxani = standard Mancano dati di safety a lungo termine per somministrate trastuzumab in associazione ad antracicline

Definiamo la risposta come pCR? Si No La paziente e’ stata trattata con AC x 4  docetaxel x 4 + trastuzumab Sottoposta a quadrantectomia + svuotamento del cavo ascellare. EI: CDIS. Infiltrazione cancerigna di 1/16 ln esaminati Definiamo la risposta come pCR? Si No

The literature has included several definitions of pCR as well as several attempts to design a sliding scale of pathologic response in order to avoid the limitations of a dichotomous endpoint (overly simplistic– residual disease Δ from near pCR to frank resistance) Sahoo and Lester. Arch Pathol Lab Med 2009

Definition of pCR NSABP B27: Surgical specimens with no invasive cancer in the breast were considered to be a pathologic complete response (pCR) Mazouni et al. J Clin Oncol 2007

Outcome according to the pathological status of the breast and the axilla When there is no residual invasive cancer in the breast, the number of involved axillary lymph nodes is inversely related to survival (NSABP-B27) Bear et al. J Clin Oncol 2006 Patients who convert to node-negative status after treatment have excellent survival, even if there is residual disease (RD) in the breast Hennessy et al. J Clin Oncol 2005

Neo-ALTTO: pCR and total pCR Total pCR= breast + axilla

La risposta al trattamento neoadiuvante puo’ essere definita pCR

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no yes unk